Lyons J M
Department of Infectious Diseases, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA 91010, USA.
Drugs Today (Barc). 2006 Mar;42 Suppl A:83-97.
The two major aims of this thesis were firstly, to provide a basis for an integrated approach to study the oculogenital biovar of Chlamydia trachomatis in order to explain the complex and varied course of female genital tract infection; and secondly, to use the understanding gained through this approach to suggest possible intervention strategies. To accomplish this end, the projects conducted and reported upon in the thesis fall into four categorical sections. Part I of the thesis addresses the bacterial factors that contribute to the pathogenesis of infection using both in vitro observations and an in vivo experimental murine model. In Part II, host immunogenetic factors are analyzed using gene knockout mice and single nucleotide polymorphism (SNP) analysis of human genes. In Part III, the efficacy of prophylactic intervention on the susceptibility and course of female genital tract infection with C. trachomatis in the mouse is evaluated. Finally, in Part IV, the natural immune response to the pathogen and the relationship that these responses have on conferring protection and/or contributing to the pathology of disease are investigated to bring us closer to the ultimate protective intervention strategy: a vaccine against C. trachomatis. This article summarizes the aims and results of the thesis, followed by a general discussion and conclusions.
本论文的两个主要目标,其一,为研究沙眼衣原体眼生殖生物变种提供一种综合方法的基础,以解释女性生殖道感染复杂多样的病程;其二,利用通过该方法获得的认识提出可能的干预策略。为实现这一目标,论文中开展并报告的项目分为四个类别部分。论文的第一部分使用体外观察和体内实验小鼠模型,探讨导致感染发病机制的细菌因素。在第二部分中,利用基因敲除小鼠和人类基因的单核苷酸多态性(SNP)分析来分析宿主免疫遗传因素。在第三部分,评估预防性干预对小鼠沙眼衣原体感染女性生殖道易感性和病程的效果。最后,在第四部分,研究对病原体的天然免疫反应以及这些反应在提供保护和/或导致疾病病理方面的关系,以使我们更接近最终的保护性干预策略:一种针对沙眼衣原体的疫苗。本文总结了论文的目标和结果,随后进行了一般性讨论和得出结论。